The important role of certain "high risk" types of human papillomaviruses (HPV's) in the etiology of cervical cancer is well-established. However, the contributions of possible intervening factors in the progression of high-risk HPV-related lesions, such as psychosocial, immune, and neuroendocrine functioning, are virtually unexplored. The proposed project aims to examine these issues in a group of women with mild dysplastic lesions of the cervix due to infection with HPV subtypes with high oncogenic potential. Ongoing research by members of this team has explored the effects of coping style and psychosocial interventions on adaptation and adherence to cervical cancer screening protocols in women at high risk for cervical cancer. The present study will extend this work by examining the interrelations among psychological, immune, and neuroendocrine factors in a sample of potentially high risk subjects and exploring the implications of these factors for health status and disease progression. Following baseline colposcopic biopsy, subjects will be assessed at notification of their biopsy status and one and two weeks following notification. Follow-up assessments will be conducted at 6-month, one- year, eighteen-month and two-year intervals. We will obtain relevant psychosocial measures (depression, hopelessness, life stress, daily hassles, social support, and loneliness) as well as measures of cellular immune function (T-cell numbers and subsets; NK cell numbers, functional activity and cytotoxity; response to mitogen stimulation; and local immune function), neuroendocrine function (cortisol secretion), and medical outcome (HPV type, histologic evidence of regression, persistence, or progression of cervical lesions). In addition, the effects of the patients' demographic, medical history, and behavioral risk factor profile will be assessed. The short-term goals of this project are to examine hypotheses about the relations among psychological variables, immunologic variables, neuroendocrine variables, and medical outcomes in women with high risk HPV infection who are being monitored but not receiving treatment. These relations will be explored both cross-sectionally via regression analyses and longitudinally via repeated measures analyses of variance and covariance, while controlling for the impact of relevant risk factors and behaviors (e.g., smoking, sexual behavior, nutrition, exercise, sleep, alcohol and drug use). The long-term goals are to develop a predictive model of disease and to identify mechanisms of progression. Such understanding will help delineate the implications of psychoneuroimmunologic factors for cervical dysplasia and enable us to target individuals at high risk, so that tailored screening and preventive protocols can be devised.